The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder.
Citalopram
Cortico-limbic brain areas
Emotional processing
Major depressive disorder
TRPC inhibition
Journal
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
ISSN: 1873-7862
Titre abrégé: Eur Neuropsychopharmacol
Pays: Netherlands
ID NLM: 9111390
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
07
04
2022
revised:
14
10
2022
accepted:
17
10
2022
pubmed:
8
11
2022
medline:
7
12
2022
entrez:
7
11
2022
Statut:
ppublish
Résumé
Abnormal emotional processing in major depressive disorder (MDD) has been associated with increased activation to negative stimuli in cortico-limbic brain regions. The authors investigated whether treatment with BI 1358894, a small-molecule inhibitor of the transient receptor potential cation channel subfamily C leads to attenuated activity in these areas in MDD patients. 73 MDD patients were randomized to receive a single oral dose of BI 1358894 (100 mg), citalopram (20 mg), or matching placebo. Brain responses to emotional faces and scenes were investigated using functional magnetic resonance imaging. Primary endpoints were BOLD signal changes in response to negative faces in cortico-limbic brain regions, i.e. bilateral amygdala (AMY), dorsolateral prefrontal cortex, anterior insula (AI), and anterior cingulate cortex. Secondary endpoints were BOLD signal changes in response to negative scenes. For each region, separate ANOVA models were computed for the comparison of treatments (BI 1358894 or citalopram) vs. placebo. The adjusted treatment differences in the % BOLD signal changes in the faces task showed that BI 1358894 induced signal reduction in bilateral AMY and left AI. In the scenes task, BI 1358894 demonstrated significant signal reduction in bilateral AMY, AI, anterior cingulate cortex and left dorsolateral prefrontal cortex. Citalopram failed to induce any significant reductions in BOLD signal in both tasks. BI 1358894-mediated inhibition of the transient receptor potential cation channel subfamily resulted in strong signal reduction in cortico-limbic brain regions, thereby supporting development of this mechanism of action for MDD patients.
Identifiants
pubmed: 36343427
pii: S0924-977X(22)00885-9
doi: 10.1016/j.euroneuro.2022.10.009
pii:
doi:
Substances chimiques
Citalopram
0DHU5B8D6V
Transient Receptor Potential Channels
0
Banques de données
ClinicalTrials.gov
['NCT03854578']
Types de publication
Randomized Controlled Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
44-51Informations de copyright
Copyright © 2022. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of Competing Interest SJ, VS, RF, SM, CT, CSchu and AWun are employees of Boehringer Ingelheim International GmbH. SG and CSschm have served as consultants to and received research support from Boehringer Ingelheim International GmbH. CP and LH are consultants for Boehringer Ingelheim International GmbH. CB and MM are employees of SBGneuro contracted to perform the blinded analysis. CK, IN, CB, MM, and AWei have no conflicts to disclose.